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Clomiphene (Clomid, Serophene) is one of the first agents used for ovulation induction in patients with infertility. Clomiphene is a synthetic hormone that binds to the estrogen receptor at the level of the hypothalamus and prevents the estrogen molecule from binding to its own receptor. This is perceived by the hypothalamus as estrogen levels being low in the system. In response, the hypothalamus releases GnRH (gonadotropin-releasing hormone), which in turn prompts the pituitary gland to release an exaggerated amount of FSH (follicle-stimulating hormone). As happens in a natural cycle, the increased secretion of FSH stimulates the development of the follicles, ultimately resulting in ovulation. The growing follicles secrete estrogen into the bloodstream, thus closing the feedback circle that the hypothalamus initiated in response to the anti-estrogenic properties of clomiphene.

Administration of clomiphene citrate enhances the normal cyclical pattern of follicular development and ovulation. If initiated as early as day 2 or day 3 of the menstrual cycle, it usually induces ovulation on day 13 or 14 of a regular 28-day cycle. If administered later, such as on day 5, ovulation could occur as late as day 16 or 17, and the length of the cycle may be extended. If the ovarian response is not appropriate on the starting dose of clomiphene, the dosage may be increased to achieve optimal stimulation. In some cases, HCG can be administered once ultrasound examinations and hormonal evaluations confirm optimal follicular development. In such cases ovulation will usually occur about 36-40 hours later.

Dr. Bayrak currently uses clomiphene for two distinct clinical indications. First indication is in women with irregular cycles due to irregular ovulation who need ovulation induction and the second one is in those who have regular cycles and need superovulation (ovulating from more than one mature egg). The goal of the treatment in women with a history irregular ovulation (commonly due to polycystic ovary syndrome – PCOS) is to make her ovulate from one mature egg. This can be accomplished in up to 80% of patients with various doses of Clomid. In the remaining 20% of patients who do not ovulate on Clomid, injectable FSH medication is necessary. The initial dose is 50mg orally for five days and if ovulation does not occur it can be increased up to 250mg daily for five days especially in resistant cases or overweight or obese women. Most commonly prescribed dose is 50-100mg daily for 5 days. Some of the side effects are headaches, bloating, mood swings and rarely visual changes and abdominal discomfort.

In patients who are ovulating regularly, Clomid is used for superovulation and the common dosage is 100mg daily for five days. In most case, two eggs mature and are released at the time of ovulation, which increases the risk of twin pregnancy to approximately 5%, if pregnancy is achieved. Pregnancy rates are quite variable based on female age and other factors affecting fertility.

Major advantages of clomiphene are its relatively low cost and the fact that it can be taken orally instead of injections. However, the effect on follicular development and ovulation are much less than injectable medications. Patients may develop 1 to 3 dominant follicles on average while on clomiphene. It may have an adverse effect on the endometrium resulting in a thin lining in some cases that may require additional treatment with estrogens.

Download Dr. Bayrak’s published findings on this issue:


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